Chiral Diaminopyrrolic Receptors for Selective Recognition of Mannosides, Part 1: Design, Synthesis, and Affinities of Second-Generation Tripodal Receptors

A new generation of chiral tripodal receptors for recognition of carbohydrates, featuring trans-1,2-diaminocyclohexane as a key structural element, and their recognition properties toward a set of glycosides of biologically relevant monosaccharides is described. The introduction of a chelating diamino unit into the pyrrolic tripodal architecture markedly enhanced their binding abilities compared with the parent aminopyrrolic receptors previously reported by our group. In addition, the chirality of the structure had a clear impact on affinities, as well as on selectivities, displaying high enantiodiscrimination levels. These second-generation diaminopyrrolic tripodal receptors are highly selective for mannose among other monosaccharides, with two members of the family being selective for the alpha and the beta anomers respectively. The measured affinities in acetonitrile, 83 mu m of (S)-7 for the beta mannoside and 127 mm of (R)-5 for the alpha mannoside, make them the most effective synthetic receptors for mannosides reported to date. The affinity assessment required a further evolution of the BC500 parameter, a previously developed binding descriptor, which in its ultimate formulation has now been extended to include, with no restrictions, complexes of any stoichiometry, and can thus be generally employed to rank affinity data from heterogeneous systems on a common scale.